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“Over the next ten years, I see a “seismic” shift in how new cancer treatments will be developed and evaluated in clinical trials. I believe that randomized trials that seek to minimize the effects of disease heterogeneity will be recognized as not being able to lead to significant advances in the treatment of cancer patients. Instead, there will be a movement toward smaller trials in targeted patient groups. These groups will be selected or at least enriched with the patients most likely to benefit from a particular treatment because of the expression of a potential therapeutic target. These targets will be identified by techniques such as genomic analysis that is increasingly rapid and affordable thanks to a new generation of sequencers or more specific molecular imaging techniques. Similarly, the efficiency of the treatments will be established by the early demonstration of modulation of the target and by highlighting the cascading effects of this modulation of the target. As data accumulates on cellular events and when cellular biomarkers, serum proteomic signatures or molecular imaging signatures demonstrate that they are valid predictors of response and influence both the duration and quality of life, we will progressively move towards a molecular medicine that is personalized, adapted, informed and guided by these new techniques. This medicine will leave the domain of research to be used in every day clinical practice.” There is an iconic Australian movie entitled The Castle. Many of its classic lines have entered into the Australian vernacular. One of them pertains to the likelihood of an improbable event. It is; “He’s dreaming”. When I wrote the forecast above, I was clearly dreaming. Although elements of my predictions are closer, it is a future that still hasn’t been realized in large measure. As we approach the end of the second decade of the twenty-first century it is pertinent to look back on the momentous changes that have occurred in the practice of oncology since the beginning of this millennium and to contemplate the changes that might still be to come in the field and how they might impact the practice of cancer imaging. Although the direct clinical impact of the revolution in genomic analysis of cancers, exemplified by The Cancer Genome Atlas (TCGA), has been questioned [1], there can be no doubt that understanding of the biological basis of cancer has improved immeasurably as a result. Thousands of articles describing the key mutations in a wide array of malignancies have been published. Over the past 2 decades, most of the key oncogenic pathways have been intimately detailed. Small molecule inhibitors of aberrant gene expression have provided effective treatments for a number of cancers that previously lacked therapeutic options once they had become metastatic. These have included treatments both for rather indolent tumours, like gastrointestinal stromal tumour (GIST), and for aggressive malignancies, like melanoma. Despite the effectiveness of drugs like imatinib in GIST [2] and vemurafenib in melanoma [3, 4], not all cells respond to treatment and development of resistance is almost universal after a time. Molecular imaging played a key role in identifying that rapid changes occur in glycolytic metabolism with successful abrogation of signaling driven by oncogenes including mutant cKit in GIST [5] and vemurafenib in BRAF-V600E melanoma [6]. This, in turn, led to further Correspondence: rod.hicks@petermac.org The Sir Peter MacCallum Department of Oncology, the University of Melbourne, Level 5, VCCC Building, 305 Grattan St, Melbourne, VIC 3000, Australia

2020 vision or myopia? A personal perspective on the future of cancer imaging and an introduction to the sequels to the “How I Read Series”